EP1672676A2 - Vorrichtung und Verfahren zur Verbesserung der Ionenerzeugung - Google Patents

Vorrichtung und Verfahren zur Verbesserung der Ionenerzeugung Download PDF

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Publication number
EP1672676A2
EP1672676A2 EP05020143A EP05020143A EP1672676A2 EP 1672676 A2 EP1672676 A2 EP 1672676A2 EP 05020143 A EP05020143 A EP 05020143A EP 05020143 A EP05020143 A EP 05020143A EP 1672676 A2 EP1672676 A2 EP 1672676A2
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EP
European Patent Office
Prior art keywords
matrix
ion source
ion
gas
axis
Prior art date
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Withdrawn
Application number
EP05020143A
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English (en)
French (fr)
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EP1672676A3 (de
Inventor
Jean-Luc Truche
Jian Bai
Timothy Joyce
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Agilent Technologies Inc
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Agilent Technologies Inc
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Filing date
Publication date
Application filed by Agilent Technologies Inc filed Critical Agilent Technologies Inc
Publication of EP1672676A2 publication Critical patent/EP1672676A2/de
Publication of EP1672676A3 publication Critical patent/EP1672676A3/de
Withdrawn legal-status Critical Current

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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/161—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission using photoionisation, e.g. by laser
    • H01J49/164—Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI]
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • H01J49/0468—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components with means for heating or cooling the sample
    • H01J49/0477—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components with means for heating or cooling the sample using a hot fluid

Definitions

  • the invention relates generally to the field of mass spectrometry and more particularly toward an ion enhancement system that provides a heated gas flow to enhance analyte ions in an atmospheric pressure matrix assisted laser desorption/ionization (AP-MALDI) mass spectrometer.
  • AP-MALDI atmospheric pressure matrix assisted laser desorption/ionization
  • the techniques have also had success on a broad based level of compounds including peptides, proteins, carbohydrates, oligosaccharides, natural products, cationic drugs, organoarsenic compounds, cyclic glucans, taxol, taxol derivatives, metalloporphyrins, porphyrins, kerogens, cyclic siloxanes, aromatic polyester dendrimers, oligodeoxynucleotides, polyaromatic hydrocarbons, polymers and lipids.
  • compounds including peptides, proteins, carbohydrates, oligosaccharides, natural products, cationic drugs, organoarsenic compounds, cyclic glucans, taxol, taxol derivatives, metalloporphyrins, porphyrins, kerogens, cyclic siloxanes, aromatic polyester dendrimers, oligodeoxynucleotides, polyaromatic hydrocarbons, polymers and lipids.
  • the analyte and matrix is applied to a metal probe or target substrate.
  • the solvent evaporates, the analyte and matrix co-precipitate out of solution to form a solid solution of the analyte in the matrix on the target substrate.
  • the co-precipitate is then irradiated with a short laser pulse inducing the accumulation of a large amount of energy in the co-precipitate through electronic excitation or molecular vibration of the matrix molecules.
  • the matrix dissipates the energy by desorption, carrying along the analyte into the gaseous phase. During this desorption process, ions are formed by charge transfer between the photo-excited matrix and analyte.
  • the MALDI technique of ionization is performed using a time-of-flight analyzer, although other mass analyzers such as an ion trap, an ion cyclotron resonance mass spectrometer and quadrupole time-of-flight are also used. These analyzers, however, must operate under high vacuum, which among other things may limit the target throughput, reduce resolution, capture efficiency, and make testing targets more difficult and expensive to perform.
  • AP-MALDI a technique referred to as AP-MALDI.
  • This technique employs the MALDI technique of ionization, but at atmospheric pressure.
  • the MALDI and the AP-MALDI ionization techniques have much in common. For instance, both techniques are based on the process of pulsed laser beam desorption/ionization of a solid-state target material resulting in production of gas phase analyte molecular ions.
  • the AP-MALDI ionization technique does not rely on a pressure differential between the ionization chamber and the mass spectrometer to direct the flow of ions into the inlet orifice of the mass spectrometer.
  • AP-MALDI can provide detection of a molecular mass up to 10 6 Da from a target size in the attamole range.
  • levels of sensitivity become increasingly important.
  • Various structural and instrument changes have been made to MALDI mass spectrometers in an effort to improve sensitivity. Additions of parts and components, however, provides for increased instrument cost.
  • attempts have been made to improve sensitivity by altering the analyte matrix mixed with the target.
  • the present invention relates to an apparatus and method for use with a mass spectrometer.
  • the invention provides an ion enhancement system for providing a heated gas flow to enhance analyte ions produced by a matrix based ion source and detected by a detector.
  • the mass spectrometer of the present invention provides a matrix based ion source for producing analyte ions, an ion detector downstream from the matrix based ion source for detecting enhanced analyte ions, an ion enhancement system interposed between the ion source and the ion detector for enhancing the analyte ions, and an ion transport system adjacent to or integrated with the ion enhancement system for transporting the enhanced analyte ions from the ion enhancement system to the detector.
  • the method of the present invention comprises producing analyte ions from a matrix based ion source, enhancing the analyte ions with an ion enhancement system, and detecting the enhanced analyte ions with a detector.
  • adjacent means, near, next to or adjoining. Something adjacent may also be in contact with another component, surround the other component, be spaced from the other component or contain a portion of the other component. For instance, a capillary that is adjacent to a conduit may be spaced next to the conduit, may contact the conduit, may surround or be surrounded by the conduit, may contain the conduit or be contained by the conduit, may adjoin the conduit or may be near the conduit.
  • conduit refers to any sleeve, transport device, dispenser, nozzle, hose, pipe, plate, pipette, port, connector, tube, coupling, container, housing, structure or apparatus that may be used to direct a heated gas or gas flow toward a defined region in space such as an ionization region.
  • the "conduit” may be designed to enclose a capillary or portion of a capillary that receives analyte ions from an ion source.
  • the term should be interpreted broadly, however, to also include any device, or apparatus that may be oriented toward the ionization region and which can provide a heated gas flow toward or into ions in the gas phase and/or in the ionization region.
  • the term could also include a concave or convex plate with an aperture that directs a gas flow toward the ionization region.
  • the term "enhance” refers to any external physical stimulus such as heat, energy, light, or temperature change, etc.. that makes a substance more easily characterized or identified.
  • a heated gas may be applied to "enhance” ions.
  • the ions increase their kinetic energy, potentials or motions and are declustered or vaporized. Ions in this state are more easily detected by a mass analyzer. It should be noted that when the ions are "enhanced", the number of ions detected is enhanced since a higher number of analyte ions are sampled through a collecting capillary and carried to a mass analyzer or detector.
  • Ion source refers to any source that produces analyte ions. Ion sources may include other sources besides AP-MALDI ion sources such as electron impact (herein after referred to as El), chemical ionization (CI) and other ion sources known in the art.
  • AP-MALDI electron impact
  • CI chemical ionization
  • the term “ion source” refers to the laser, target substrate, and target to be ionized on the target substrate.
  • the target substrate in AP-MALDI may include a grid for target deposition. Spacing between targets on such grids is around 1-10 mm. Approximately 0.5 to 2 microliters is deposited on each site on the grid.
  • the term "ionization region" refers to the area between the ion source and the collecting capillary.
  • the term refers to the analyte ions produced by the ion source that reside in that region and which have not yet been channeled into the collecting capillary.
  • This term should be interpreted broadly to include ions in, on, about or around the target support as well as ions in the heated gas phase above and around the target support and collecting capillary.
  • the ionization region in AP MALDI is around 1-5 mm in distance from the ion source (target substrate) to a collecting capillary (or a volume of 1-5 mm).
  • the distance from the target substrate to the conduit is important to allow ample gas to flow from the conduit toward the target and target substrate. For instance, if the conduit is too close to the target or target substrate, then arcing takes place when voltage is applied. If the distance is too far, then there is no efficient ion collection.
  • an "ion enhancement system” refers to any device, apparatus or components used to enhance analyte ions. The term does not include directly heating a capillary to provide conductive heat to an ion stream.
  • an "ion enhancement system” comprises a conduit and a gas source.
  • An ion enhancement system may also include other devices well known in the art such as a laser, infrared red device, ultraviolet source or other similar type devices that may apply heat or energy to ions released into the ionization region or in the gas phase.
  • ion transport system refers to any device, apparatus, machine, component, capillary, that shall aid in the transport, movement, or distribution of analyte ions from one position to another.
  • the term is broad based to include ion optics, skimmers, capillaries, conducting elements and conduits.
  • matrix based refers to an ion source or mass spectrometer that does not require the use of a drying gas, curtain gas, or desolvation step. For instance, some systems require the use of such gases to remove solvent or cosolvent that is mixed with the analyte. These systems often use volatile liquids to help form smaller droplets. The above term applies to both nonvolatile liquids and solid materials in which the sample is dissolved. The term includes the use of a cosolvent. Cosolvents may be volatile or nonvolatile, but must not render the final matrix material capable of evaporating in vacuum.
  • Such materials would include, and not be limited to m-nitrobenzyl alcohol (NBA), glycerol, triethanolamine (TEA), 2,4-dipentylphenol,1,5-dithioffirietol/dierythritol (magic bullet), 2-nitrophenyl octyl ether (NPOE), thioglycerol, nicotinic acid, cinnamic acid, 2,5-dihydroxy benzoic acid (DHB), 3,5 ⁇ dimethoxy-4-hydroxycinnamic acid (sinpinic acid), a-cyano-4-hydroxycinnamic acid (CCA), 3-methoxy-4-hydroxycinnamic acid (ferulic acid), monothioglycerol, carbowax, 2-(4-hydroxyphenylazo)benzoic acid (HABA), 3,4-dihydroxycinnamic acid (caffeic acid), 2-amino-4-methyl-5-nitropvridine with their cosolvents and derivatives
  • gas flow refers to any gas that is directed in a defined direction in a mass spectrometer.
  • the term should be construed broadly to include monatomic, diatomic, triatomic and polyatomic molecules that can be passed or blown through a conduit.
  • the term should also be construed broadly to include mixtures, impure mixtures, or contaminants.
  • the term includes both inert and non-inert matter. Common gases used with the present invention could include and not be limited to ammonia, carbon dioxide, helium, fluorine, argon, xenon, nitrogen, air etc..
  • gas source refers to any apparatus, machine, conduit, or device that produces a desired gas or gas flow. Gas sources often produce regulated gas flow, but this is not required.
  • capillary or “collecting capillary” shall be synonymous and will conform with the common definition(s) in the art.
  • the term should be construed broadly to include any device, apparatus, tube, hose or conduit that may receive ions.
  • detector refers to any device, apparatus, machine, component, or system that can detect an ion. Detectors may or may not include hardware and software. In a mass spectrometer the common detector includes and/or is coupled to a mass analyzer.
  • a “plurality” is at least 2, e.g., 2, 3, 4, 6, 8, 10, 12 or greater than 12.
  • the phrases "a plurality of and “multiple” are used interchangeably.
  • a plurality of conduits or gas streams contains at least a first conduit or gas stream and a second conduit or gas stream, respectively.
  • FIG. 1 shows a general block diagram of a mass spectrometer.
  • the block diagram is not to scale and is drawn in a general format because the present invention may be used with a variety of different types of mass spectrometers.
  • a mass spectrometer 1 of the present invention comprises an ion source 3, an ion enhancement system 2, an ion transport system 6 and a detector 11.
  • the ion enhancement system 2 may be interposed between the ion source 3 and the ion detector 11 or may comprise part of the ion source 3 and/or part of the ion transport system 6.
  • the ion source 3 may be located in a number of positions or locations.
  • a variety of ion sources may be used with the present invention.
  • El, CI or other ion sources well known in the art may be used with the invention.
  • the ion enhancement system 2 may comprise a conduit 9 and a gas source 7. Further details of the ion enhancement system 2 are provided in FIGS 2-3. The ion enhancement system 2 should not be interpreted to be limited to just these two configurations or embodiments.
  • the ion transport system 6 is adjacent to the ion enhancement system 2 and may comprise a collecting capillary 7 or any ion optics, conduits or devices that may transport analyte ions and that are well known in the art.
  • FIG. 2 shows a cross-sectional view of a first embodiment of the invention.
  • the figure shows the present invention applied to an AP-MALDI mass spectrometer system.
  • the figure shows the invention with a source housing 14.
  • the use of the source housing 14 to enclose the ion source and system is optional. Certain parts, components and systems may or may not be under vacuum. These techniques and structures are well known in the art.
  • the ion source 3 comprises a laser 4, a deflector 8 and a target support 10.
  • a target 13 is applied to the target support 10 in a matrix material well known in the art.
  • the laser 4 provides a laser beam that is deflected by the deflector 8 toward the target 13.
  • the target 13 is then ionized and the analyte ions are released as an ion plume into an ionization region 15.
  • the ionization region 15 is located between the ion source 3 and the collecting capillary 5.
  • the ionization region 15 comprises the space and area located in the area between the ion source 3 and the collecting capillary 5.
  • This region contains the ions produced by ionizing the sample that are vaporized into a gas phase.
  • This region can be adjusted in size and shape depending upon how the ion source 3 is arranged relative to the collecting capillary 5.
  • located in this region are the analyte ions produced by ionization of the target 13.
  • the collecting capillary 5 is located downstream from the ion source 3 and may comprise a variety of material and designs that are well known in the art.
  • the collecting capillary 5 is designed to receive and collect analyte ions produced from the ion source 3 that are discharged as an ion plume into the ionization region 15.
  • the collecting capillary 5 has an aperture and/or elongated bore 12 that receives the analyte ions and transports them to another capillary or location.
  • the collecting capillary 5 is connected to a main capillary 18 that is under vacuum and further downstream.
  • the collecting capillary 5 may be supported in place by an optional insulator 17. Other structures and devices well known in the art may be used to support the collecting capillary 5.
  • the conduit 9 provides a flow of heated gas toward the ions in the ionization region 15.
  • the heated gas interacts with the analyte ions in the ionization region 15 to enhance the analyte ions and allow them to be more easily detected by the detector 11 (not shown in FIG. 2).
  • These ions include the ions that exist in the heated gas phase.
  • the detector 11 is located further downstream in the mass spectrometer (see FIG. 1).
  • the conduit 9 may comprise a variety of materials and devices well known in the art.
  • the conduit 9 may comprise a sleeve, transport device, dispenser, nozzle, hose, pipe, pipette, port, connector, tube, coupling, container, housing, structure or apparatus that is used to direct a heated gas or gas flow toward a defined region in space or location such as the ionization region 15. It is important to the invention that conduit 9 be positioned sufficiently close to the target 13 and the target support 10 so that a sufficient amount of heated gas can be applied to the ions in the ionization region 15.
  • the gas source 7 provides the heated gas to the conduit 9.
  • the gas source 7 may comprise any number of devices to provide heated gas. Gas sources are well known in the art and are described elsewhere.
  • the gas source 7 may be a separate component as shown in FIGS 2-3 or may be integrated with a coupling 23 (shown in FIG. 4) that operatively joins the collecting capillary 5, the conduit 9 and the main capillary 18.
  • the gas source 7, may provide a number of gases to the conduit 9.
  • gases such as nitrogen, argon, xenon, carbon dioxide, air, helium etc.. may be used with the present invention.
  • the gas need not be inert and should be capable of carrying a sufficient quantum of energy or heat.
  • Other gases well known in the art that contain these characteristic properties may also be used with the present invention.
  • FIG. 3 shows a cross sectional view of a second embodiment of the present invention.
  • the conduit 9 may be oriented in any number of positions to direct gas toward the ionization region 15.
  • FIG. 3 in particular shows the conduit 9 in detached mode from the collecting capillary 5. It is important to the invention that the conduit 9 be capable of directing a sufficient flow of heated gas to provide enhancement to the analyte ions located in the ionization region 15.
  • the conduit 9 can be positioned from around 1- 5 mm in distance from the target 13 or the target support 10.
  • the heated gas applied to the target 13 and the target support 10 should be in the temperature range of about 60-150 degrees Celsius.
  • the gas flow rate should be approximately 2-15 L/minute.
  • a ion source of the invention may contain an axis of ion movement defined by the longitudinal axis of the ion collection capillary, i.e., the ion collection capillary comprises a longitudinal axis that the ions move along.
  • the axis of heated gas flow is defined by the longitudinal axis of the conduit that provides the heated gas, i.e., a molecular axis that the heated gas moves along.
  • the axis of gas flow may be at any angle from 0° and 360 °, including the angles of 0° and 360°, relative to the axis of ion movement from the target substrate to the entrance of the ion collection capillary.
  • the axis of gas flow may be opposing or anti-parallel (i.e. about 180 degrees), parallel (i.e., about 0 degrees) or orthogonal to the axis of ion flow, or any angle therebetween.
  • the axis of heated gas is at any angle in the following ranges: of 0-30 degrees, 30-60 degrees, 60-90 degrees, 90-120 degrees, 120-150 degrees, 150-180 degrees, 180-210 degrees, 210-240 degrees, 240-270 degrees, 270-300 degrees, 300-330 degrees, 330-360 degrees with respect to the axis of ion flow.
  • the axis heated gas is oriented orthogonally to the axis of ion movement.
  • the angles listed above may be any angle in two or three dimensional space.
  • the angle may be in an x/y plane (i.e., in the same plane as Fig. 3), or in a z plane (i.e., the axis of heated gas may be oriented above or below the x/y plane of Fig. 3) or a combination therof.
  • the axis of heated gas may be at any angle relative to the axis of ion transport.
  • FIGS 2 and 4-7 illustrate the first embodiment of the invention.
  • the conduit 9 is designed to enclose the collecting capillary 5.
  • the conduit 9 may enclose all of the collecting capillary 5 or a portion of it. However, it is important that the conduit 9 be adjacent to the collecting capillary end 20 so that heated gas can be delivered to the analyte ions located in the ionization region 15 before they enter or are collected by the collecting capillary 5.
  • FIGS 1-6 and 8 show only a few embodiments of the present invention and are employed for illustrative purposes only. They should not be interpreted as narrowing the broad scope of the invention.
  • the conduit 9 may be a separate component or may comprise a part of the coupling 23.
  • FIGS. 4-6 show the conduit 9 as a separate component.
  • FIGS 4-6 show coupling 23 and its design for joining the collecting capillary 5, the main capillary 18, and the conduit 9.
  • the coupling 23 is designed for attaching to a fixed support 31 (shown in FIGS. 7 and 8).
  • the coupling 23 comprises a spacer 33, a housing 35, and a capillary cap 34 (See FIG. 5).
  • the capillary cap 34 and the spacer 33 are designed to fit within the housing 35.
  • the spacer 33 is designed to apply pressure to the capillary cap 34 so that a tight seal is maintained between the capillary cap 34 and the main capillary 18.
  • the capillary cap 34 is designed to receive the main capillary 18.
  • a small gap 36 is defined between the spacer 33 and the capillary cap 34 (Sec FIG. 6). The small gap 36 allows gas to flow from the gas source 7 into the collecting capillary 5 as opposed to out of the housing 35 as is accomplished with prior art devices.
  • An optional centering device 40 may be provided between the collecting capillary 5 and the conduit 9.
  • the centering device 40 may comprise a variety of shapes and sizes. It is important that the centering device 40 regulate the flow of gas that is directed into the ionization region 15.
  • FIGS. 4-6 show the centering device as a triangular plastic insert. However, other designs and devices may be employed between the conduit 9 and the collecting capillary 5.
  • the detector 11 is located downstream from the ion source 3 and the conduit 9.
  • the detector 11 may be a mass analyzer or other similar device well known in the art for detecting the enhanced analyte ions that were collected by the collecting capillary 5 and transported to the main capillary 18.
  • the detector 11 may also comprise any computer hardware and software that are well known in the art and which may help in detecting enhanced analyte ions.
  • a matrix-based ion source may contain a device for directing a plurality of streams of heated gas (e.g., at least a first and second streams of heated gas) towards the ionization region of the ion source.
  • the device may contain multiple (e.g., at least a first and second) orifices (e.g., nozzles) for directing the streams of heated gas towards the ionization region, and those orifices may be arranged around the ionization region.
  • the orifices may be equidistant from the ionization region.
  • a matrix-based ion source of the invention may contain a target substrate, an ion collection capillary, an ionization region that is interposed between the target plate and the ion collecting capillary, a first conduit for directing a first stream of heated gas to the ionization region; and a second conduit for directing a second stream of heated gas to the ionization region.
  • the matrix-based ion source may further comprise an axis of ion movement defined by the longitudinal axis of the ion collection capillary, and first and second axes of gas flow defined by the first and second conduits. The first and second axes of gas flow may be at any angle relative to the axes of ion movement, as described above.
  • the device may provide a plurality of streams of heated gas (e.g., at least first and second streams of heated gas) that are oriented at any angle with respect to the direction of ion flow from the target plate to the ion collection capillary (which, as described above, is the same as the longitudinal axis of the collection capillary).
  • the streams of heated gas are oriented orthogonally to the direction of ion flow (e.g., parallel to the surface of the target substrate), and the streams of heated gas enter the ionization region from the side.
  • the streams of heated gas may be at any angle relative to the z axis of the same space.
  • the device may contain multiple orifices for directing a plurality of streams of heated gas towards the ionization region.
  • the device may contain multiple conduits oriented towards the ionization region, each conduit terminating in an orifice.
  • the device may contain a single gas transport element containing multiple orifices that are positioned around the ionization region.
  • the gas transport element may form an open or closed ring around or above the ionization region, and the orifices of the gas transport element may be positioned to direct a plurality of streams of gas towards the ionization region.
  • a device for providing a plurality of streams of heated gas directed towards the ionization region of an ion source may contain multiple conduits (e.g., at least 2, 3, 4 or 5 or more conduits) each having a longitudinal axis oriented towards the ionization region.
  • the longitudinal axis of the conduits may be oriented orthogonally relative to the direction of ion flow (e.g., parallel to the surface of the target support).
  • a device may contain an open or closed ring-shaped gas transport element containing multiple orifices (e.g., at least 2, 3, 4 or 5 or more orifices) that direct gas in the direction of the ionization region.
  • the gas transport element may be positioned above the ionization region or surrounding the ionization region.
  • the device provides a plurality of gas streams that contact the ionization region from any direction, including from the side (i.e., orthogonally) or any oblique angle relative to the direction of ion flow.
  • FIG. 7 shows a cross sectional view of a device.
  • the collecting capillary 5 is connected to the main capillary 18 by the capillary cap 34.
  • the capillary cap is designed for receiving the main capillary 18 and is disposed in the housing 35.
  • the housing 35 connects directly to the fixed support 31.
  • the gas source 7 provides the gas through the channels 38 defined between the housing 35 and the capillary cap 34. The gas flows from the gas source 7 into the channel 38 through a passageway 24 and then into an ionization chamber 30. The gas is released into the ionization chamber 30 and serves no purpose at this point.
  • FIG. 8 shows a cross sectional view of the first embodiment of the present invention, with the conduit 9 positioned between the ion source 3 and the gas source 7.
  • the conduit 9 operates to carry the heated gas from the gas source 7 to the collecting capillary end 20.
  • the method of the present invention produces enhanced analyte ions for ease of detection in the mass spectrometer 1.
  • the method comprises heating analyte ions located in the ionization region 15 adjacent to the collecting capillary 5 with a directed gas to make them more easily detectable by the detector 11.
  • Gas is produced by the gas source 7, directed through the channels 38 and the small gap 36. From there the gas is carried into an annular space 42 defined between the conduit 9 and the collecting capillary 5.
  • the heated gas then contacts the optional centering device 40 (not shown in FIG.
  • the centering device 40 is disposed between the collecting capillary 5 and the conduit 9 and shaped in a way to regulate the flow of gas to the ionization region 15. Gas flows out of the conduit 9 into the ionization region 15 adjacent to the collecting capillary end 20. The analyte ions in the ionization region 15 are heated by the gas that is directed into this region. Analyte ions that are then enhanced are collected by the collecting capillary 5, carried to the main capillary 18 and then sent to the detector 11. It should be noted that after heat has been added to the analyte ions adjacent to the source, the detection limits and signal quality improve dramatically. This result is quite unexpected.
  • the invention provides a method for producing analyte ions using a matrix-based ion source.
  • This method involves directing a plurality of streams of heated gas (e.g., a first and a second stream of heated gas) to the ionization region of the ion source, ionizing a sample to produce analyte ions; and transporting the resultant analyte ions out of the ion source.
  • heated gas e.g., a first and a second stream of heated gas
  • a Bruker Esquire-LC ion trap mass spectrometer was used for AP-MALDI studies.
  • the mass spectrometer ion optics were modified (one skimmer, dual octapole guide with partitioning) and the ion sampling inlet of the instrument consisted of an ion sampling capillary extension with a conduit concentric to a capillary extension.
  • the ion sampling inlet received a gas flow of 4-10 L/min. of heated nitrogen.
  • a laser beam (337.1 nm, at 10 Hz) was delivered by a 400 micron fiber through a single focusing lens onto the target. The laser power was estimated to be around 50 to 70 uj.
  • the data was obtained by using Ion Charge Control by setting the maximum trapping time to 300 ms (3 laser shots) for the mass spectrometer scan spectrum. Each spectrum was an average of 8 micro scans for 400 to 2200 AMU.
  • the matrix used was an 8 mM aIpha-cyano-4-hydroxy-cinnamic acid in 25% methanol, 12% TPA, 67% water with 1% acetic acid.
  • Matrix targets were premixed and 0.5 ul of the matrix/target mixture was applied onto a gold plated stainless steel target. Targets used included trypsin digest of bovine serum albumin and standard peptide mixture containing angiotensin I and IT, bradykinin, and fibrinopeptide A.
  • FIG. 9 shows the results without the addition of heated gas to the target or ionization region. The figure does not show the existence of sharp peaks (ion enhancement) at the higher m/z ratios.
  • FIG. 10 shows the results with the addition of the heated gas to the target in the ionization region.
  • the figure shows the existence of the sharp peaks (ion enhancement) at the higher m/z ratios.

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EP05020143A 2004-12-16 2005-09-15 Vorrichtung und Verfahren zur Verbesserung der Ionenerzeugung Withdrawn EP1672676A3 (de)

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US11/015,190 US7132670B2 (en) 2002-02-22 2004-12-16 Apparatus and method for ion production enhancement

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EP1672676A2 true EP1672676A2 (de) 2006-06-21
EP1672676A3 EP1672676A3 (de) 2008-07-09

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US20050151091A1 (en) * 2002-02-22 2005-07-14 Jean-Luc Truche Apparatus and method for ion production enhancement
US7132670B2 (en) * 2002-02-22 2006-11-07 Agilent Technologies, Inc. Apparatus and method for ion production enhancement
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